MicroRNA profiling of hepatocarcinogenesis identifies C19MC cluster as a novel prognostic biomarker in hepatocellular carcinoma
Liver International, 04/13/2012Augello C et al.
C19MC cluster is a novel molecular alteration characteristic of liver cancer and predictor of poor prognosis. C19MC is an attractive candidate for novel hepatocellular carcinoma (HCC) therapies.
The authors used a low-density array platform to profile the expression of 664 mature miRNAin a cohort of 60 hepatitis Cvirus-positive liver lesions representative of all stages of progressive hepatocarcinogenesis.
They validated selected miRNA in two independent patient series by qPCRand they characterized the genomic status of the mi RNAcluster C19MCby fluorescent in situ hybridization and copy-number variation analyses.
A 18-miRNA signature distinguished cirrhosis, dysplastic nodules and HCC lesions.
Four miRNAs overexpressed in HCCs belonged to chromosome 19 miRNA cluster (C19MC).
Significant overexpression of C19MC in early HCC compared to dysplastic nodules could be confirmed in a second series of hepatitis Bvirus-related liver lesions (n = 30).
In a third series of 61 HCCs, C19MCcluster was overexpressed in HCCs compared to matched cirrhotic parenchyma and regardless of the type of viral infection.
High C19MCmiRNAlevels were correlated with poor clinico-pathological features, increased risk of tumour recurrence and shorter overall survival time.
HCCs overexpressing the C19MCcluster showed genetic amplification of the corresponding locus.
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